OM Prognosis

OM Prognostic Indicators

Several clinical, pathological, and genetic prognostic factors have been identified as being associated with higher risk of developing metastatic ocular melanoma (OM). Higher risk of metastasis is associated with large tumor size, ciliary body involvement, orange pigment overlying the tumor and older patient age. Pathological findings such as epithelioid (versus spindle) morphology, is also associated with higher risk of metastasis. Unlike melanomas of the skin, a tumor staging system is not widely used by ocular oncologists. OM rarely spreads through the lymph system, instead it is more likely to spread hemotogenously, or through the blood.

Chromosomal Abnormality

Recent molecular genetic research has shed light on chromosomal alterations, gene expression patterns and the relationship between these patterns and overall prognosis. The most widely used predictor of metastatic disease in Europe is the detection of monosomy 3. About 20% of tumors without chromosome 3 deletion have a poor prognosis. Gains on chromosomes 6 and 8 can help refine the predictive value of monosomy 3 – gain of 6p indicating a better prognosis and gain of 8q indicating a worse prognosis. This information can help predict risk of developing metastatic disease and can be obtained from a fine needle biopsy at the time of treatment of the primary eye tumor.

New Gene Mutation Discovered: BAP1

It appears that the loss of chromosome 3 is related to a new genetic finding – BAP1 (BRCA associated protein 1). If BAP1 is mutated or inactivated in a tumor (often found in tumors with a higher risk of metastasis) and the 2ndcopy is deleted (e.g. when there is loss of one copy of chromosome 3), then this confers a higher risk of metastasis. This is a newly defined mutation and research is ongoing to understand the relationship between this finding and treatments for OM. Interestingly, this mutation has also been identified in a cancer called mesothelioma. Researchers in both fields are coming together to learn more about this mutation.

Gene Expression Patterns

the most widely used predictor of metastatic disease in the United States is gene expression profiling. Using a different laboratory technique, gene expression patterns of the tumor biopsy can also be used to predict prognosis. Specifically, about half of ocular melanomas are shown to be “class 1” tumors. These tumors exhibit a distinct gene expression pattern, rarely undergo loss of chromosome 3, and have a very low risk of metastasis. In contrast, the other half of ocular melanomas fall into the “class 2” category which exhibit a different gene expression pattern, usually have lost one copy of chromosome 3, and are at a very high risk of metastasis.

OM Metastasis

Metastatic melanoma (also known as stage IV) is a general term for the spreading of cancer beyond its original site. The liver is the most common site of metastasis in ocular melanoma. Among those who develop metstatic disease, 90% of patients develop liver disease. However, ocular melanoma can spread to any organ in the body. After the liver, common sites include the lung, bones and brain. Even though the cancer cells have spread to other parts of the body, since the cells remain melanoma cells, this cancer is called metastatic melanoma.

Approximately 50% of ocular melanoma patients will develop metastatic disease within 15 years of the original diagnosis, and once the liver is involved, the cancer is currently incurable. However, if metastatic disease is found early there are a few localized and systemic treatment options that may extend life expectancy and help improve quality of life for patients.

Surveillance:

Currently, there is no consensus regarding type or frequency of scans following diagnosis and treatment of the primary eye tumor. It is important to speak with your doctors to decide what is right for you. Of the patients who develop metastatic disease, more than 90% of patients will develop liver metastases, the majority of surveillance techniques are focused on the liver. These include: abdominal magnetic resonance imaging (MRI), abdominal ultrasound and liver function tests. The scientific community is currently working to develop guidelines, but until then, each patient must take into consideration their individual clinical situation and discuss appropriate surveillance with their doctors.